Abstract : Our ideas of the pathogenesis of diabetes mellitus have changed considerably during the past 40 years. Our current concept result from the acquisition of new data on the role of the central nervous and endocrine systems in the pathogenesis of diabetes mellitus; new data on the metabolic processes taking place in it; and, finally, the elicitation of processes in the picture of this disease which attest to the injury to the organism in the absence of insulin, and the reactions which characterize its control of the inflicted injury. While 40 years ago it was considered universally accepted that diabetes mellitus develops basically as the result of pancreatic insufficiency, it is impossible at the present time to visualize the pathogenesis of diabetes mellitus without taking into account also the role of other endocrine glands especially that of the anterior hypophyseal lobe, the suprarenal glands, cerebral cortex, and hypothalamus.